Category:

Dateline:

Public Company Information:

NASDAQ:

ALXN

NEW HAVEN, Conn.--(BUSINESS WIRE)--Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced the
initiation of two Phase 3 trials of ALXN1210, a highly innovative,
longer-acting anti-C5 antibody that inhibits terminal complement. The
first trial is a Phase 3 open-label, multinational, active-controlled
study of ALXN1210 compared to eculizumab (Soliris®) in
complement inhibitor treatment-naïve patients with paroxysmal nocturnal
hemoglobinuria (PNH). Alexion has also accelerated the initiation of a
registration trial of ALXN1210 in patients with atypical hemolytic
uremic syndrome (aHUS). This second trial is a Phase 3, open-label,
single arm, multinational trial to evaluate the safety and efficacy of
ALXN1210 in complement inhibitor treatment-naïve adolescent and adult
patients with aHUS. Both studies will evaluate ALXN1210 administered
intravenously every eight weeks. Alexion expects to begin enrolling
patients into these trials later this year, and plans to initiate a
Phase 3 trial of ALXN1210 in pediatric patients with aHUS in 2017.

Alexion has also commenced dosing of a new formulation of ALXN1210
administered subcutaneously in healthy volunteers in a Phase I study.

“With more than 20 years of expertise in the discovery and development
of complement inhibitors, our ongoing commitment is to bring even higher
levels of innovation to patients with devastating ultra-rare diseases,”
said Martin Mackay, Ph.D., Executive Vice President and Global Head of
R&D at Alexion. “We are very pleased with our agreement with global
regulators to progress ALXN1210 into Phase 3 studies in patients with
PNH and aHUS and are now working with investigators to enroll patients
into the registration studies with urgency.”

About the ALXN1210 PNH Study

The PNH trial is a Phase 3, randomized, open-label, active-controlled,
multicenter 26-week study to evaluate the safety and efficacy of
ALXN1210 compared to eculizumab in complement inhibitor treatment-naïve
patients with PNH. The co-primary endpoints are the normalization of
lactate dehydrogenase (LDH) levels and the percentage of patients who
achieve transfusion avoidance (TA). Secondary endpoints include
percentage change from baseline in LDH levels, change from baseline in
quality of life as assessed by the Functional Assessment of Chronic
Illness Therapy (FACIT)-Fatigue, and percentage of patients with
stabilized hemoglobin. The study is designed to evaluate the
non-inferiority of ALXN1210 compared to eculizumab.

Patients in the ALXN1210 arm will receive a single loading dose of
ALXN1210, followed by regular maintenance dosing every 8 weeks based on
3 weight cohorts. Patients in the eculizumab arm will receive 4 weekly
induction doses, followed by regular maintenance dosing every 2 weeks.
The multinational study will enroll approximately 214 adults (≥ 18 years
of age) with a diagnosis of PNH who have never been treated with a
complement inhibitor.

About the ALXN1210 aHUS Study

The aHUS trial is a Phase 3, open-label, single arm, multicenter 26-week
study to evaluate the safety and efficacy of ALXN1210 in complement
inhibitor treatment-naïve adolescent and adult patients with aHUS. The
primary endpoint is complete thrombotic microangiopathy (TMA) response
at 26 weeks. Secondary endpoints include dialysis requirement status,
complete TMA response over time, observed value and change from baseline
in estimated glomerular filtration rate, and change from baseline in
chronic kidney disease stage, all evaluated at 26 weeks; time to
complete TMA response; and additional efficacy measures. Patients will
receive a single loading dose of ALXN1210, followed by regular
maintenance dosing every 8 weeks based on 3 weight cohorts.

The multinational study will enroll approximately 55 adolescent (12 to <
18 years of age) and adult (≥ 18 years of age) patients with aHUS who
have never been treated with a complement inhibitor.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is an ultra-rare blood disorder in which chronic, uncontrolled
activation of complement, a component of the normal immune system,
results in hemolysis (destruction of the patient's red blood cells). PNH
strikes people of all ages, with an average age of onset in the early
30s.1 Approximately 10 percent of all patients first develop
symptoms at 21 years of age or younger.5 PNH develops without
warning and can occur in men and women of all races, backgrounds and
ages. PNH often goes unrecognized, with delays in diagnosis ranging from
one to more than 10 years.6 In the period of time before
Soliris® (eculizumab) was available, it had been estimated
that approximately one-third of patients with PNH did not survive more
than five years from the time of diagnosis.7 PNH has been
identified more commonly among patients with disorders of the bone
marrow, including aplastic anemia (AA) and myelodysplastic syndromes
(MDS).8,9,10 In patients with thrombosis of unknown origin,
PNH may be an underlying cause.11

About aHUS

aHUS is a chronic, ultra-rare, and life-threatening disease in which a
life-long and permanent genetic deficiency in one or more complement
regulatory genes causes chronic uncontrolled complement activation,
resulting in complement-mediated thrombotic microangiopathy (TMA), the
formation of blood clots in small blood vessels throughout the body.2,3
Permanent, uncontrolled complement activation in aHUS causes a life-long
risk for TMA, which leads to sudden, catastrophic, and life-threatening
damage to the kidney, brain, heart, and other vital organs, and
premature death.2,4 Prior to the availability of Soliris,
seventy-nine percent of all patients with aHUS died, required kidney
dialysis or had permanent kidney damage within three years after
diagnosis despite plasma exchange or plasma infusion (PE/PI).12
Moreover, 33 to 40 percent of patients died or progressed to end-stage
renal disease with the first clinical manifestation of aHUS despite
PE/PI.12,13 Prior to the availability of Soliris, the
majority of patients with aHUS who received a kidney transplant commonly
experienced subsequent systemic TMA, resulting in a 90 percent
transplant failure rate in these TMA patients.14

aHUS affects both children and adults. Complement-mediated TMA also
causes reduction in platelet count (thrombocytopenia) and red blood cell
destruction (hemolysis). While mutations have been identified in at
least ten different complement regulatory genes, mutations are not
identified in 30-50 percent of patients with a confirmed diagnosis of
aHUS.12,14,15

About ALXN1210

ALXN1210 is a highly innovative, longer-acting anti-C5 antibody
discovered and developed by Alexion that inhibits terminal complement.
In early studies, ALXN1210 demonstrated rapid, complete, and sustained
reduction of free C5 activity.16 Alexion has completed
enrollment in two ongoing clinical studies of ALXN1210 in patients with
PNH—a Phase 1/2 dose-escalating study and an open-label, multi-dose
Phase 2 study that is also evaluating longer dosing intervals beyond 8
weeks.

ALXN1210 is currently in Phase 3 trials in patients with PNH and aHUS.
In addition, Alexion is conducting a Phase 1 study to evaluate a new
formulation of ALXN1210 administered subcutaneously in healthy
volunteers.

In June 2016, the European Commission granted Orphan Drug Designation
(ODD) to ALXN1210 for the treatment of patients with PNH.

About Soliris®(eculizumab)

Soliris is a first-in-class terminal complement inhibitor developed from
the laboratory through regulatory approval and commercialization by
Alexion. Soliris is approved in the U.S. (2007), European Union (2007),
Japan (2010) and other countries as the first and only treatment for
patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce
hemolysis. PNH is a debilitating, ultra-rare and life-threatening blood
disorder, characterized by complement-mediated hemolysis (destruction of
red blood cells). Soliris is also approved in the U.S. (2011), European
Union (2011), Japan (2013) and other countries as the first and only
treatment for patients with atypical hemolytic uremic syndrome (aHUS) to
inhibit complement-mediated thrombotic microangiopathy, or TMA (blood
clots in small vessels). aHUS is a debilitating, ultra-rare and
life-threatening genetic disorder characterized by complement-mediated
TMA. Soliris is not indicated for the treatment of patients with
Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS). For
the breakthrough medical innovation in complement inhibition, Alexion
and Soliris have received some of the pharmaceutical industry's highest
honors: the Prix Galien USA (2008, Best Biotechnology Product) and
France (2009, Rare Disease Treatment).

More information, including the full U.S. prescribing information, on
Soliris is available at www.soliris.net.

Important Safety Information

The U.S. product label for Soliris includes a boxed warning:
“Life-threatening and fatal meningococcal infections have occurred in
patients treated with Soliris. Meningococcal infection may become
rapidly life-threatening or fatal if not recognized and treated early
[see Warnings and Precautions (5.1)]. Comply with the most current
Advisory Committee on Immunization Practices (ACIP) recommendations for
meningococcal vaccination in patients with complement deficiencies.
Immunize patients with a meningococcal vaccine at least two weeks prior
to administering the first dose of Soliris, unless the risks of delaying
Soliris therapy outweigh the risk of developing a meningococcal
infection. [See Warnings and Precautions (5.1) for additional guidance
on the management of the risk of meningococcal infection]. Monitor
patients for early signs of meningococcal infections and evaluate
immediately if infection is suspected. Soliris is available only through
a restricted program under a Risk Evaluation and Mitigation Strategy
(REMS). Under the Soliris REMS, prescribers must enroll in the program
[see Warnings and Precautions (5.2)]. Enrollment in the Soliris REMS
program and additional information are available by telephone:
1-888-SOLIRIS (1-888-765-4747).”

In patients with PNH, the most frequently reported adverse events
observed with Soliris treatment in clinical studies were headache,
nasopharyngitis (runny nose), back pain and nausea. Soliris treatment of
patients with PNH should not alter anticoagulant management because the
effect of withdrawal of anticoagulant therapy during Soliris treatment
has not been established. In patients with aHUS, the most frequently
reported adverse events observed with Soliris treatment in clinical
studies were headache, diarrhea, hypertension, upper respiratory
infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough,
peripheral edema, nausea, urinary tract infections, and pyrexia. Soliris
is not indicated for the treatment of patients with Shiga-toxin E.
coli-related hemolytic uremic syndrome (STEC-HUS). Please see full
prescribing information for Soliris, including BOXED WARNING regarding
risk of serious meningococcal infection.

AboutAlexion

Alexion is a global biopharmaceutical company focused on developing and
delivering life-transforming therapies for patients with devastating and
rare disorders. Alexion is the global leader in complement inhibition
and has developed and commercializes the first and only approved
complement inhibitor to treat patients with paroxysmal nocturnal
hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), two
life-threatening ultra-rare disorders. In addition, Alexion’s metabolic
franchise includes two highly innovative enzyme replacement therapies
for patients with life-threatening and ultra-rare disorders,
hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D).
Alexion is advancing the most robust rare disease pipeline in the
biotech industry with highly innovative product candidates in multiple
therapeutic areas. This press release and further information about
Alexion can be found at: www.alexion.com.

[ALXN-G]

Forward-Looking Statement

This press release contains forward-looking statements, including
statements related to Alexion's development plans for ALXN1210, the
medical benefits of ALXN1210 for the treatment of PNH and aHUS, medical
and commercial potential of ALXN1210, and plans for regulatory filings
for ALXN1210. Forward-looking statements are subject to factors that may
cause Alexion's results and plans to differ from those expected,
including for example, decisions of regulatory authorities regarding
marketing approval or material limitations on the marketing of our
products, delays, interruptions or failures in the manufacture and
supply of our products and our product candidates, progress in
establishing and developing commercial infrastructure, failure to
satisfactorily address matters raised by the FDA and other regulatory
agencies, the possibility that results of clinical trials are not
predictive of safety and efficacy results of our products in broader
patient populations in the disease studied or other diseases, the risk
that strategic transactions will not result in short-term or long-term
benefits, the possibility that current results of commercialization are
not predictive of future rates of adoption of Soliris in PNH, aHUS or
other diseases, the possibility that clinical trials of our product
candidates could be delayed or that additional research and testing is
required by regulatory agencies, including for ALXN1210, the adequacy of
our pharmacovigilance and drug safety reporting processes, the risk that
third party payors (including governmental agencies) will not reimburse
or continue to reimburse for the use of our products at acceptable rates
or at all, risks regarding government investigations, including
investigations of Alexion by the SEC and DOJ, the risk that anticipated
regulatory filings are delayed, including for ALXN1210, the risk that
estimates regarding the number of patients with PNH, aHUS, HPP and LAL-D
are inaccurate, the risks of shifting foreign exchange rates, and a
variety of other risks set forth from time to time in Alexion's filings
with the U.S. Securities and Exchange Commission, including but not
limited to the risks discussed in Alexion's Quarterly Report on Form
10-Q for the period ended June 30, 2016 and in our other filings with
the U.S. Securities and Exchange Commission. Alexion does not intend to
update any of these forward-looking statements to reflect events or
circumstances after the date hereof, except when a duty arises under law.

Caprioli J, Noris M, Brioschi S, et al; for the International
Registry of Recurrent and Familial HUS/TTP. Genetics of HUS: the
impact of MCP, CFH, and IF mutations on clinical presentation,
response to treatment, and outcome. Blood. 2006;108:1267-1279.